Sourced

• Nothing, believe me, nothing is more satisfying to me personally than getting a great idea and then beatin' it to death.
  • Late Night with David Letterman (5 March 1993)

• We're told that they were zealots fueled by religious fervour.. religious fervour and if you live to be a thousand years old will that make any sense to you? Will that make any goddamn sense?
  • During his first show after the September 11th attacks (17 September 2001)

• What is this, Vassar?!
  • The Wahoo Gazette (30 October 2002)

• In My Pants!
  • The Wahoo Gazette (30 October 2002)

• I may not be smart enough to debate you point-for-point on this, but I have the feeling about 60% of what you say is crap.
  • To Bill O'Reilly, in discussion about the supposed War on Christmas, as quoted in "In Letterman appearance, O'Reilly repeated false claim that school changed 'Silent Night' lyrics", Media Matters for America, (2006-01-04)

• Now all of us can talk to the NSA — just by dialing any number.
  • On the National Security Agency's eavesdropping program, on The Late Show with David Letterman, Monologue (25 January 2006)

• Hey John, I got a question! You need a ride to the airport?
  • The Late Show with David Letterman (24 September 2008), while watching a live feed of Katie Couric interviewing with John McCain in the CBS studio; McCain had just canceled his scheduled appearance on Letterman's show that evening, telling him he needed to return to Washington immediately and deal with the economic crisis, quoted in "The David Letterman-John McCain smackdown" by Gary Susman at Popwatch (25 September 2009)

• Nice job… What the hell is U2 supposed to play?
  • To Paul Shaffer, after the CBS Orchestra played "Pride (In the Name of Love)", The Late Show with David Letterman (5 March 2009), during U2's week-long guest appearance.

• How long have you been a black man?
  • To US President Barack Obama, after he had responded to a question on whether he thought racism was fueling criticisms of him with the comment "First of all, I think it's important to realize that I was actually black before the election.", as quoted in "Obama Takes On Letterman" by Michael D. Shear, in The Washington Post (22 September 2009)

Unsourced

• I think you can use some of those words on TV. But one thing you can't do is throw coffee, i've said it over and over again!
  • The Late Show with David Letterman, following a confrontation between comedian Andy Kaufman and wrestler Jerry Lawler.

• Letterman: Did you inhale?

President Obama: Well, I thought that was the point.

• on allegations that Barack Obama smoked marijuana in the past